Abstract
Background aims
Roux en y anastomosis is a preferred method of biliary reconstruction in liver transplantation
that involves living donors or pediatric patients. However, biliary stricture is a
frequent and serious complication, accounting for up to 40% of biliary complications
in these patients. Previously, we demonstrated that extraluminal delivery of adipose-derived
(AD) mesenchymal stromal cells (MSCs) decreased peri-biliary fibrosis and increased
neo-angiogenesis in a porcine model of duct-to-duct biliary anastomosis. In this study,
we used a porcine model of Roux en y anastomosis to evaluate the beneficial impact
of a novel intraluminal MSC delivery system.
Methods
Nine animals were divided into three groups: no stent (group 1), bare stent (group
2) and stent coated with AD-MSCs (group 3). All animals underwent cholecystectomy
with roux en y choledochojejunostomy. Two animals per group were followed for 4 weeks
and one animal per group was followed for 8 weeks. Cholangiograms and blood were sampled
at baseline and the end of study. Biliary tissue was collected and examined by Masson
trichrome staining and immunohistochemical staining for MSC markers (CD34 and CD44)
and for neo-angiogenesis (CD31).
Results
Two of three animals in group 1 developed an anastomotic site stricture. No strictures
were observed in the animals of group 2 or group 3. CD34 and CD44 staining showed
that AD-MSCs engrafted successfully at the anastomotic site by intraluminal delivery
(group 3). Furthermore, biliary tissue from group 3 showed significantly less fibrosis
and increased angiogenesis compared with the other groups.
Conclusions
Intraluminal delivery of AD-MSCs resulted in successful biliary engraftment of AD-MSCs
as well as reduced peri-biliary fibrosis and increased neo-angiogenesis.
Key Words
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Article info
Publication history
Published online: February 25, 2023
Accepted:
January 27,
2023
Received:
August 21,
2022
Publication stage
In Press Corrected ProofIdentification
Copyright
© 2023 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.